A pilot study on peptidylarginine deiminases and protein deimination in animal cancers across vertebrate species

Inal, Jameel, Hristova, Mariya and Lange, Sigrun (2022) A pilot study on peptidylarginine deiminases and protein deimination in animal cancers across vertebrate species. International Journal of Molecular Sciences, 23 (15). pp. 1-27. ISSN 1422-0067

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Official URL: https://doi.org/10.3390/ijms23158697

Abstract / Description

PADs are a group of calcium-dependent enzymes that play key roles in inflammatory pathologies and have diverse roles in cancers. PADs cause irreversible post-translational modification of arginine to citrulline, leading to changes in protein function in different cellular compartments. PAD isozyme diversity differs throughout phylogeny in chordates, with five PAD isozymes in mammals, three in birds, and one in fish. While the roles for PADs in various human cancers are mounting (both in regards to cancer progression and epigenetic regulation), investigations into animal cancers are scarce. The current pilot-study therefore aimed at assessing PAD isozymes in a range of animal cancers across the phylogeny tree. In addition, the tissue samples were assessed for total protein deimination and histone H3 deimination (CitH3), which is strongly associated with human cancers and also indicative of gene regulatory changes and neutrophil extracellular trap formation (NETosis). Cancers were selected from a range of vertebrate species: horse, cow, reindeer, sheep, pig, dog, cat, rabbit, mink, hamster, parrot, and duck. The cancers chosen included lymphoma, kidney, lung, testicular, neuroendocrine, anaplastic, papilloma, and granulosa cell tumour. Immunohistochemical analysis revealed that CitH3 was strongly detected in all of the cancers assessed, while pan-deimination detection was overall low. Both PAD2 and PAD3 were the most predominantly expressed PADs across all of the cancers assessed, while PAD1, PAD4, and PAD6 were overall expressed at lower, albeit varying, levels. The findings from this pilot study provide novel insights into PAD-mediated roles in different cancers across a range of vertebrate species and may aid in the understanding of cancer heterogeneity and cancer evolution.

Item Type: Article
Additional Information: ** From MDPI via Jisc Publications Router
Uncontrolled Keywords: peptidylarginine deiminase (PAD); deimination/citrullination; deiminated histone H3 (CitH3); cancer; cancer evolution; phylogeny
Subjects: 500 Natural Sciences and Mathematics > 570 Life sciences; biology
500 Natural Sciences and Mathematics > 590 Animals (Zoology)
Department: School of Human Sciences
SWORD Depositor: Pub Router
Depositing User: Pub Router
Date Deposited: 12 Aug 2022 14:19
Last Modified: 12 Aug 2022 14:19
URI: https://repository.londonmet.ac.uk/id/eprint/7848


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